The long term objective of the research described in this proposal is the development of models and associated computational tools for the elucidation of selectivity in organic reactions. Our aim is to assist the synthetic chemist in the rational design of practical synthetic strategies for the construction of complex molecules, among them pharmaceuticals. The present models are distinct from other theoretical methods which have previously been employed by the synthetic community, in particular, the frontier molecular orbital (FMO) model. It assesses chemical reactivity and selectivity on the basis of energetic considerations, in contrast to the FMO model which employs topological arguments. Completed applications, to the stereochemistry of electrophilic and nucleophilic additions and to the regio- and diastereofacial selectivity in Diels-Alder cycloadditions, have demonstrated the ability of the approach to reproduce known reaction selectivities. Proposed applications, to the stereochemistry of addition of complex reagents and to selectivity in 1,3-dipolar cycloadditions, will not only further development of the models but in addition will expose new chemistry of potential import to the formulation of novel synthetic strategies.